The health consequences and medical costs associated with cigarette smoking are extremely well established. There are now more than 50,000 studies linking cigarette smoking to increased morbidity and mortality from cardiovascular diseases, various forms of cancer, and chronic obstructive lung diseases. It is estimated that annually in the United States, smoking is causually related to 170,000 deaths from cardiovascular disease, 130,000 deaths from cancer, and 50,000 deaths from chronic obstructive lung disease. As many as one third of heavy smokers who are now 35 years old will die before age 85 of diseases caused by their smoking. The estimated cost of health problems associated with smoking, including medical care, absenteeism, decreased work productivity, and accidents is estimated to be $56 billion per year.
Given the consistent demonstration of dose-dependent relationships between smoking and disease, evidence of reductions in health risks following smoking cessation, and experimental studies documenting carcinogenic effects of tobacco smoke in animals, few scientists question the causal nature of the relationship between smoking and illness. Despite this, approximately 26% of the adults in the United States continue to smoke. Very few effective strategies for smoking cessation have been developed, and up to 80% of smokers who initially stop smoking will relapse within six months to a year. The potential success of smoking cessation efforts is impeded, in part, by the fact that many of the advantages of continuing to smoke are immediate while the disadvantages of smoking are delayed and probabilistic.
One immediate consequence of quitting smoking is weight gain. There is overwhelming evidence that smoking cessation leads to weight gain. The 1988 Surgeon General's Report (USPHS, 1988) reported on the results of 28 cross-sectional evaluations of smoking and body weight as well as 43 studies that evaluated smoking and body weight status over time. Of the 71 studies evaluated, 62 (87%) collectively indicated that smokers weigh less than nonsmokers and that people who quit smoking gain weight. For the cross-sectional studies, it was reported that smokers weighed an average of 7.13 lb (range: 2.36-14.99 lb) more than nonsmokers. Smokers who quit in the longitudinal studies gained an average of 6.16 lb (range: 1.76-18.07 lb) following cessation. A popular, but erroneous, statistic is that only about one third of smokers will gain weight following cessation, while one third stay the same weight and one third lose weight. Unfortunately, recent studies have confirmed that the overwhelming majority of smokers gain weight following cessation.
Unfortunately, weight gain following smoking cessation appears to be a significant reason for continued smoking. At least one third of smokers report that they continue to smoke primarily for the weight-related benefits. It also appears that some individuals, particularly females, are likely to initiate smoking because of the weight reduction properties of cigarettes. Weight-related concerns also appear to be an important predictor of success in both worksite and pharmacologic intervention.
Although weight and weight-related concerns appear to be a major reason for continued smoking, it may be surprising to learn that there are few effective treatment methods for reducing this inevitable weight gain. Behavioral methods, which are effective in weight control in general, have not yet been developed to the extent where they can prevent, or even reduce, postcessation weight gain. In terms of pharmacologic-intervention, some investigators have advocated the use of nicotine chewing gum to aid in reducing postcessation weight gain. Reports of its effectiveness are variable, with nicotine chewing gum being clearly effective only if (a) the individual is a heavy smoker and (b) the individual uses large amounts of nicotine chewing gum. Also, a significant percentage of those using nicotine gum will continue to do so up to one year after smoking cessation. As such, its use as an aid to primarily reduce postcessation weight gain has been questioned.
Given these findings, there is a need to test both pharmacologic and non-pharmacologic methods to reduce postcessation weight gain. A promising drug product for this purpose is phenylpropanolamine (ppa). In addition to its appetite suppressant effects, phenylpropanolamine has been shown to increase metabolic rate in laboratory animals. The observation of increased metabolic rate is an important contribution given the strong evidence that smokers have elevated metabolic rates relative to nonsmokers.
U.S. Pat. No. 4,255,439 discloses a means and method for aiding individuals to stop tobacco smoking and lose overweight by administering a combination of an imidazoline derivative with an anorectic. The preferred imidazoline derivative is 2-(2,6-dichlorophenylamine)-2-imidazoline hydrochloride (clonidine hydrochloride), and the preferred anorectic is phentermine resin. Phenylpropanolamine is mentioned as an anorectic that can be used in place of the phentermine resin.
U.S. Pat. No. 4,639,368 discloses a chewing gum composition for supplying a medicament orally, which medicament is capable of being absorbed through the buccal cavity. The composition comprises a medicament, for example phenylpropanolamine and a carbon dioxide generator. Phenylpropanolamine is disclosed as an example of a medicament which is utilized as an anorectic or as a decongestant.